The specific goal of this research will be to determine the three-dimensional geometries, to the maximum accuracy possible, of several proteins and their complexes with substrate analogs, inhibitors and cofactors. The technique to the bemployed is single-crystal x-ray diffraction. The study has as its long range goal an understanding of the mechanism of enzyme and action, specificity, and the structural basis of differential drug affinity for differing species of the sam eenzyme. Among the proteins to be studied in particular are yeast cytochrome c peroxidase, cytochrome P450 from Pseudomonas putida and several species of dihydrofolate reductase.